Age-related decrement in hormone-stimulated lipolysis

The ability of hormones to activate responses in a variety of tissues decreases with age. The mechanism(s) responsible for these alterations are unclear. We have confirmed that the ability of a beta-adrenergic receptor agonist to activate lipolysis in isolated rat adipocytes decreases with age. Maximum response to isoproterenol was greater in 2-mo-old rats (600 +/- 30 nmol of glycerol released/10(5) cells per h) than 12-mo-old rats (250 +/- 25 nmol/10(5) cells per h), P less than 0.001. Similarly, ACTH is less effective in activating lipolysis in the adipocytes from the older rats. However, the cAMP analogue 8-(4-chlorophenothio)adenosine 3',5'-monophosphate cyclic activated lipolysis equally in the two groups, suggesting that the deficit in adipocytes from the older rats was proximal to cAMP-dependent protein kinase activation. Both isoproterenol and ACTH were significantly less effective in promoting cAMP accumulation in adipocytes isolated from 12-mo-old rats. There was no difference in phosphodiesterase activity of the adipocytes between the two groups. beta-Adrenergic receptors were measured using the antagonist radioligand [125I]cyanopindolol. The number of beta-adrenergic receptors was actually increased in the adipocytes from 12-mo-old rats (26,000 +/- 2,600 receptors/cell) compared with cells from 2-mo-old rats (7,200 +/- 1,300 receptors/cell). The results suggest that diminished cAMP production is responsible for the diminished lipolytic response in the adipocytes of older rats. The mechanism responsible for this change is uncertain but cannot be explained by a loss in beta-adrenergic receptors.